| 摘要: |
| 目的通过观察干扰素调节因子3（IRF3）对瘢痕疙瘩成纤维细胞增殖和细胞外基质表达的作用，探讨IRF3在皮肤纤维化中的调控机制。方法取行瘢痕疙瘩切除手术的10例患者的术中切除的瘢痕疙瘩组织为研究材料，另择8例外科手术患者的正常皮肤组织为对照，培养两者的成纤维细胞。采用real-timeRT-PCR、Westernblot检测成纤维细胞IRF3mRNA、蛋白表达水平，转染siRNAs-IRF3后IRF3蛋白水平；检测TGF-茁1诱导后瘢痕疙瘩成纤维细胞增殖情况，细胞外基质Ⅰ型胶原蛋白（collagenⅠ）、a-平滑肌肌动蛋白（a-SMA）I型胶原与TGF-茁受体Ⅰ、Ⅱ，及TGF-茁1信号通路调节蛋白p-Smad2、Smad2、p-Smad3、Smad3表达水平。结果IRF3在瘢痕疙瘩组织中表达显著上调。下调IRF3的表达，显著抑制瘢痕疙瘩成纤维细胞的增殖，并抑制collagenⅠ、a-SMA的表达，同时抑制TGF-茁1诱导的瘢痕疙瘩成纤维细胞的TGF-茁受体Ⅰ、Ⅱ的表达。下调IRF3的表达亦抑制瘢痕疙瘩成纤维细胞p-Smad2、Smad2、p-Smad3、Smad3表达水平。结论IRF3表达下调通过抑制TGF-茁1/Smad信号通路，抑制瘢痕疙瘩成纤维细胞增殖和细胞外基质的表达。IRF3或为治疗瘢痕疙瘩新的靶点。 |
| 关键词: 干扰素调节因子 3 瘢痕疙瘩成纤维细胞 细胞外基质 TGF-茁1/Smad 通路 |
| DOI：10.12056/j.issn.1006-2785.2018.40.5.2017-2588 |
| 分类号: |
| 基金项目:浙江省医药卫生一般研究计划项目（2015KYB244）；浙江省教育厅高教重中之重学科（2008-255） |
|
| IRF3 regulates proliferation of fibroblasts and expression of extracellular matrix proteins in keloid |
|
|
|
the First Affiliated Hospital of Wenzhou Medical University
|
| Abstract: |
| Objective To investigate the expression of Interferon regulatory factor 3 (IRF3) in keloid, and its function in regulating proliferation of keloid-derived fibroblasts(KFs) and expression of extracellular matrix(ECM) proteins. Methods Ten tissue samples of keloid and 8 samples of normal skin were cultured and fibroblasts were isolated. The expression of IRF3 mRNA and protein in human keloid tissues were detected by qRT-PCR and Western blotting, respectively. KFs were incubated with siRNAs-IRF3 or scramble for 48 h; then cells were treated with TGF-茁1 (10 ng/ml) for 24 h. KFs proliferation, the
expression of type I collagen, a-SMA, TGF-茁 RI /II, p-Smad2, Smad2, p-Smad3 and Smad3 proteins were detected. Results
Expression of IRF3 mRNA and proterin was significantly higher in human keloid tissues than that in normal skin tissues. Down-regulation of IRF3 significantly inhibited KF proliferation and the expression of type I collagen, a-SMA, TGF-茁 receptor I and II in TGF-茁1-stimulated KFs. Furthermore, down-regulation of IRF3 suppressed the phosphorylation levels of Smad2 and Smad3 in human KFs induced by TGF-茁1. Conclusion Down-regulation of IRF3 inhibits the proliferation and ECM expression
in KFs via suppressing the TGF-茁1/Smad signaling pathway. IRF3 may represent a novel target for treatment of the keloid disease. |
| Key words: IRF3 KFs ECM TGF-茁1/Smad pathway |
